Risk factors for sports concussion : an evidence-based systematic review

Concussion is a common sports injury with approximately 1.6–3.8 million sport-related concussions reported in the USA annually. Identifying risk factors may help in preventing these injuries. This systematic review aims to identify such risk factors. Three electronic databases; ScienceDirect, PubMed and SpringerLink, were searched using the keywords ‘RISK FACTORS’ or ‘PREDISPOSITION’ in conjunction with ‘SPORT’ and ‘CONCUSSION’. Based on the inclusion and exclusion criteria, 13 628 identified titles were independently analysed by two of the authors to a final list of 86 articles. Only articles with a level of evidence of I, II and III were included according to robust study design and data analysis. The level of certainty for each risk factor was determined. A high level of certainty for increased risk of a subsequent concussion in athletes sustaining more than one previous concussion was reported in 10 of 13 studies. Further, a high level of certainty was assigned to match play with all 29 studies reporting an increased concussion risk during matches. All other risk factors were evaluated as having a low level of certainty. Although several risk factors were identified from the appraised studies, prospective cohort studies, larger sample sizes, consistent and robust measures of risk should be employed in future research.This work was supported, in part, with funds from the University of Cape Town and the South African Medical Research Council. SM was funded by the South African National Research Foundation (NRF). SA was funded jointly by the Deutscher Akademischer Austausch Dienst (DAAD) and NRF. MP was funded by the Thembakazi Trust.http://bjsm.bmj.com/hb2014ay201

An association between polymorphisms within the APOE gene and concussion aetiology in rugby union players

OBJECTIVES: Concussion refers to changes in neurological function due to biomechanical forces transmitted to the head. The APOE ε4 allele is associated with brain injury severity. The objective was to determine if APOE gene variants are associated with concussion history and severity in rugby players. DESIGN: In total, 128 non-concussed controls and 160 previously concussed participants (all cases N = 160; diagnosed N = 139) were recruited from high school (junior, N = 121), club (N = 116) and professional rugby teams (N = 51). METHODS: Participants were genotyped for rs405509 (G > T), rs429358 (T > C) and rs7412 (C > T) APOE variants. Statistical analyses were performed using the R environment. RESULTS: The rs405509 TT genotype was over-represented in controls compared to all cases (P = 0.043; control: 29%, all cases: 18%; odds ratio: 0.55, 95% confidence interval 0.31–0.98). The APOE-ε isoform frequencies were not significantly different between groups (P > 0.05). Additionally, the inferred APOE (rs405509-ε2/ε3/ε4) T-ε3 haplotype was over-represented in controls (41%) compared to diagnosed (32%, P = 0.042). The G-ε3 haplotype was under-represented in controls (36%) compared to all cases (44%, P = 0.019) and diagnosed (44%, P = 0.021). The TT genotype was significantly associated with rapid recovery (P = 0.048, <1 week: 51%, N = 70, ≥1 week: 36%, N = 29; odds ratio: 0.55, 95% confidence interval 0.30–1.01). CONCLUSIONS: These findings support the further elucidation of the APOE gene or closely-related genes in concussion aetiology. Although similar preliminary results were found when juniors were separately analysed, the under-powered sample size for junior subgroup requires future investigation in larger cohorts of junior-level athletes.The National Research Foundation (A.V.S., grant number 90942), (M.P., grant numbers 93416:2015, 85534:2015). The National Research Foundation of South Africa, the Deutscher Akademischer Austausch Dienst (DAAD) and the University of Cape Town funded S.A. and S.M.http://www.elsevier.com/locate/jsam2019-02-01hj2017Sports Medicin

Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients

Background: The prevalence of Parkinson’s disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. Methods: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2’s protein structure was investigated by molecular modelling. Results: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. Conclusions: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry

The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data

Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD

The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data

Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.This project was supported by the Global Parkinson’s Genetics Program (GP2). GP2 is funded by the Aligning Science Against Parkinson’s (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinson’s Research (https://gp2.org).Open Access funding provided by the National Institutes of Health (NIH).This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Services; project numbers ZO1 AG000535 and ZO1 AG000949, as well as the National Institute of Neurological Disorders and StrokePeer reviewe

Movement of Prion‐Like α‐Synuclein along the Gut‐Brain Axis in Parkinson’s Disease: A Potential Target of Curcumin Treatment

A pathological hallmark of the neurodegenerative disorder, Parkinson's disease (PD), is aggregation of toxic forms of the presynaptic protein, α-synuclein in structures known as Lewy bodies. α-Synuclein pathology is found in both the brain and gastrointestinal tracts of affected individuals, possibly due to the movement of this protein along the vagus nerve that connects the brain to the gut. In this review, we discuss current insights into the spread of α-synuclein pathology along the gut–brain axis, which could be targeted for therapeutic interventions. The prion-like propagation of α-synuclein, and the clinical manifestations of gastrointestinal dysfunction in individuals living with PD, are discussed. There is currently insufficient evidence that surgical alteration of the vagus nerve, or removal of gut-associated lymphoid tissues, such as the appendix and tonsils, are protective against PD. Furthermore, we propose curcumin as a potential candidate to prevent the spread of α-synuclein pathology in the body by curcumin binding to α-synuclein's non-amyloid β-component (NAC) domain. Curcumin is an active component of the food spice turmeric and is known for its antioxidant, anti-inflammatory, and potentially neuroprotective properties. We hypothesize that once α-synuclein is bound to curcumin, both molecules are subsequently excreted from the body. Therefore, dietary supplementation with curcumin over one's lifetime has potential as a novel approach to complement existing PD treatment and/or prevention strategies. Future studies are required to validate this hypothesis, but if successful, this could represent a significant step towards improved nutrient-based therapeutic interventions and preventative strategies for this debilitating and currently incurable disorder.South African National Research Foundation and South African Medical Research Council.http://www.wileyonlinelibrary.com/journal/ejn2022-05-27hj2022Neurolog

Movement of prion-like α-synuclein along the gut–brain axis in Parkinson's disease : a potential target of curcumin treatment

A pathological hallmark of the neurodegenerative disorder, Parkinson's disease (PD), is aggregation of toxic forms of the presynaptic protein, α-synuclein in structures known as Lewy bodies. α-Synuclein pathology is found in both the brain and gastrointestinal tracts of affected individuals, possibly due to the movement of this protein along the vagus nerve that connects the brain to the gut. In this review, we discuss current insights into the spread of α-synuclein pathology along the gut–brain axis, which could be targeted for therapeutic interventions. The prion-like propagation of α-synuclein, and the clinical manifestations of gastrointestinal dysfunction in individuals living with PD, are discussed. There is currently insufficient evidence that surgical alteration of the vagus nerve, or removal of gut-associated lymphoid tissues, such as the appendix and tonsils, are protective against PD. Furthermore, we propose curcumin as a potential candidate to prevent the spread of α-synuclein pathology in the body by curcumin binding to α-synuclein's non-amyloid β-component (NAC) domain. Curcumin is an active component of the food spice turmeric and is known for its antioxidant, anti-inflammatory, and potentially neuroprotective properties. We hypothesize that once α-synuclein is bound to curcumin, both molecules are subsequently excreted from the body. Therefore, dietary supplementation with curcumin over one's lifetime has potential as a novel approach to complement existing PD treatment and/or prevention strategies. Future studies are required to validate this hypothesis, but if successful, this could represent a significant step towards improved nutrient-based therapeutic interventions and preventative strategies for this debilitating and currently incurable disorder.South African National Research Foundation and South African Medical Research Council.http://www.wileyonlinelibrary.com/journal/ejn2022-05-27hj2022Neurolog

Unravelling the interaction between the DRD2 and DRD4 genes, personality traits and concussion risk

CITATION: Abrahams, S., et 2019. Unravelling the interaction between the DRD2 and DRD4 genes, personality traits and concussion risk. BMJ Open Sport and Exercise Medicine, 5(1):e000465, doi:10. 1136/bmjsem- 2018- 000465).The original publication is available at https://bmjopensem.bmj.comBackground: Concussion occurs when biomechanical forces transmitted to the head result in neurological deficits. Personality may affect the balance between safe and dangerous play potentially influencing concussion risk. Dopamine receptor D2 (DRD2) and dopamine receptor D4 (DRD4) genetic polymorphisms were previously associated with personality traits. Objectives: This case–control genetic association study investigated the associations of (1) DRD2 and DRD4 genotypes with concussion susceptibility and personality, (2) personality with concussion susceptibility and (3) the statistical model of genotype, personality and concussion susceptibility. Methods: In total, 138 non-concussed controls and 163 previously concussed cases were recruited from high school (n=135, junior), club and professional rugby teams (n=166, senior). Participants were genotyped for DRD2 rs12364283 (A>G), DRD2 rs1076560 (C>A) and DRD4 rs1800955 (T>C) genetic variants. Statistical analyses including structural equation modelling were performed using the R environment and STATA. Results: The rs1800955 CC genotype (p=0.014) and inferred DRD2 (rs12364283–rs1076560)–DRD4 (rs1800955) A–C–C allele combination (p=0.019) were associated with decreased concussion susceptibility in juniors. The rs1800955 TT and CT genotypes were associated with low reward dependence in juniors (p<0.001) and seniors (p=0.010), respectively. High harm avoidance was associated with decreased concussion susceptibility in juniors (p=0.009) and increased susceptibility in seniors (p=0.001). The model showed that a genetic variant was associated with personality while personality was associated with concussion susceptibility. Conclusion: These findings highlight the linear relationship between genetics, personality and concussion susceptibility. Identifying a genetic profile of ‘high risk’ behaviour, together with the development of personalised behavioural training, can potentially reduce concussion risk.https://bmjopensem.bmj.com/content/5/1/e000465Publisher's versio

The association between harm avoidance personality traits and self-reported concussion history in South African rugby union players

OBJECTIVES : Personality traits have been proposed to affect the risk of sports concussion, but evidence is limited. Cloninger’s Tridimensional Personality Questionnaire (TPQ) measures novelty seeking, harm avoidance (HA), and reward dependence traits. The aim of this study was to investigate the relationship between TPQ scores and concussion history in rugby union players. DESIGN : Cross-sectional study. METHODS : Rugby players from high schools, senior amateur clubs, and professional teams provided a self-reported concussion history and completed the TPQ. Participants reporting no previous concussions formed the control group, while participants reporting concussion formed the case group. A one-way analysis of covariance, with age as a covariate, was used to examine the differences in TPQ scores between groups. RESULTS : Of the 309 participants, 54% reported a minimum of one concussion (junior: 47%; amateur: 52%; professional: 72%). HA scores were significantly higher in junior players without a history of concussion compared to cases (p = 0.006). Specifically, the junior control group had higher “anticipatory worry” (p = 0.009) and “fear of uncertainty” (p = 0.008). In contrast, the professional control group had lower HA scores than cases (p = 0.009), while the amateur cohort displayed no differences between control and case groups. CONCLUSIONS : This study identified a novel association between HA and concussion in rugby players, adding evidence to the role of personality in a multifactorial risk-model of concussion. The findings suggest that lower HA may lead to increased dangerous play in youth rugby, influencing concussion susceptibility. Contrasting associations in the professional cohort suggest further research is required to understand the role of personality in concussion. Remove selectedSM and SA were funded by the South African National Research Foundation and the University of Cape Town. MP was funded by the Thembakazi Trust. This study was in part funded by the South African National Research Foundation and the University of Cape Town.http://www.elsevier.com/locate/jsam2019-01-01hj2017Sports Medicin

Inflammatory and apoptotic signalling pathways and concussion severity : a genetic association study

The objective was to investigate the relationship between IL-1B rs16944, IL-6 rs1800795, and CASP8 rs3834129 genetic polymorphisms and concussion severity. Rugby players from high school, senior amateur, and professional teams completed a concussion severity questionnaire and donated a DNA sample. Participants (n = 163) were split into symptom severity groups around the median number and duration of symptoms. The frequency of participants with high symptom counts (more than five symptoms) increased across the IL-1B (C/C: 35%; C/T: 51%; T/T: 56%; P = 0.047) and the IL-6 (C/C: 31%; C/G: 44%; G/G: 58%; P = 0.027) genotypes. The C–C inferred interleukin allele construct frequency, created from combining the IL-1B and IL-6 genotype data, was lower in participants reporting a high symptom count (18%), compared to those with a low symptom count (fewer than six symptoms, 36%, P = 0.002). Similarly, the C–C inferred interleukin allele construct frequency was lower in those reporting prolonged symptom duration (more than one week, 16%), as opposed to short symptom duration (less than one week, 34%, P = 0.015). This study provides evidence of novel inflammatory pathway genetic associations with concussion severity, which supports the hypothesis implicating neuroinflammation in the development of concussion symptoms.The National Research Foundation funded the study (A.V.S., grant number 90942), (M.P., grant numbers 93416:2015, 85534:2015). The National Research Foundation and the University of Cape Town funded S.A. and S.M.https://www.tandfonline.com/loi/rjsp202019-03-06hj2019Sports Medicin